{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T09:48:48Z","timestamp":1791884928606,"version":"4.3.4"},"reference-count":55,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T00:00:00Z","timestamp":1791849600000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82502317"],"award-info":[{"award-number":["82502317"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Gen. Psychiatry"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Antidepressants can cause extrapyramidal side effects, but their impact on Parkinson's disease (PD) risk remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>We aimed to investigate the association between genetic liability to antidepressant use and PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We examined the causal effect of antidepressant use on PD using Mendelian randomisation (MR) analysis. We further performed multivariable MR (MVMR) analysis to determine the independent effect of genetic liability to antidepressant use on PD by accounting for the effect of major depressive disorder (MDD) on PD. The United States Food and Drug Administration Adverse Event Reporting System (FAERS) database (2004 Q1\u20132024 Q2, 53.4 million event\u2010level records) was mined to assess associations between 13 antidepressants and PD. Colocalisation analyses identified shared genetic variants between genetic liability to antidepressant use and PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MR analyses demonstrated that genetic liability to antidepressant use was inversely associated with PD (odds ratio [OR]: 0.74,\n                      <jats:italic>p<\/jats:italic>\n                      \u2010false discovery rate (FDR)\u00a0=\u00a00.016), whereas MDD itself showed no causal association (OR: 1.01,\n                      <jats:italic>p<\/jats:italic>\n                      \u2010FDR\u00a0=\u00a00.934). MVMR confirmed that the inverse association between genetic liability to antidepressant use and PD was independent of genetic liability to MDD (OR: 0.69,\n                      <jats:italic>p<\/jats:italic>\n                      \u2010FDR\u00a0=\u00a00.018). Colocalisation highlighted\n                      <jats:italic>LHFPL3<\/jats:italic>\n                      ,\n                      <jats:italic>KMT2E<\/jats:italic>\n                      and\n                      <jats:italic>SRPK2<\/jats:italic>\n                      at the chromosome 7q22.3 locus as shared genetic components. Furthermore, real\u2010world FAERS data revealed that although most antidepressants (10\/13) showed no significant disproportionate reporting for PD, clomipramine and mirtazapine were associated with increased reporting odds, whereas duloxetine exhibited a significant inverse reporting signal.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Genetic and observational evidence together support an inverse association between antidepressant use and PD. Given varying individual drug profiles, agents such as duloxetine warrant further prospective evaluation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/gps3.70067","type":"journal-article","created":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T09:29:49Z","timestamp":1791883789000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Antidepressant use and Parkinson's disease risk: Overall protective effect with drug\u2010specific variation"],"prefix":"10.1002","volume":"39","author":[{"given":"Ancha","family":"Baranova","sequence":"first","affiliation":[{"name":"School of Systems Biology George Mason University  Manassas Virginia USA"},{"name":"Research Centre for Medical Genetics Russian Academy of Medical Sciences  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbao","family":"Cao","sequence":"additional","affiliation":[{"name":"School of Systems Biology George Mason University  Manassas Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxin","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Colorectal Medical Oncology Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxi","family":"Sun","sequence":"additional","affiliation":[{"name":"Suzhou Guangji Hospital  Suzhou Jiangsu China"},{"name":"Affiliated Guangji Hospital of Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongming","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3204-8191","authenticated-orcid":false,"given":"Fuquan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry The Affiliated Brain Hospital of Nanjing Medical University  Nanjing Jiangsu China"},{"name":"Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University  Nanjing Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci11121633"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/gpsych\u20102025\u2010102278"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/gpsych\u20102025\u2010102225"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2025.111258"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398\u2010024\u201003216\u2010z"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2024.111165"},{"key":"e_1_2_11_8_1","first-page":"1","article-title":"Antidepressant use among persons aged 12 and over: United States, 2011\u20132014","volume":"283","author":"Pratt LA","year":"2017","journal-title":"NCHS Data Brief"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(23)01419\u20108"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2021.05.038"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/gpsych\u20102025\u2010102405"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph18168596"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000003508"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2008.152983"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnu.12303"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0b013e3182a956ad"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531\u2010025\u201001104\u2010x"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jad.2025.120087"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787\u2010025\u201001873\u20100"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.5c00134"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000213783"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.7554\/elife.34408"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010018\u20100326\u20107"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010022\u201005473\u20108"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1474\u20104422(19)30320\u20105"},{"issue":"3","key":"e_1_2_11_26_1","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1093\/ije\/dyy258","article-title":"Improving the accuracy of two\u2010sample summary\u2010data Mendelian randomization: moving beyond the NOME assumption","volume":"48","author":"Bowden J","year":"2019","journal-title":"Int J Epidemiol"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.6048"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004383"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201010994\u2010z"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213\u2010022\u201006238\u2010x"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2016.01.004"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2008.06.045"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1684\/pnv.2025.1231"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210\u2010023\u201002818\u20106"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2017.01.066"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.62641\/aep.v52i5.1634"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041\u2010025\u201001200\u20102"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.62641\/aep.v53i3.1864"},{"issue":"13","key":"e_1_2_11_39_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms26136514","article-title":"Psychopharmacological therapy positively modulates disease activity in inflammatory bowel disease: a systematic review","volume":"26","author":"Di Vincenzo F","year":"2025","journal-title":"Int J Mol Sci"},{"issue":"3","key":"e_1_2_11_40_1","first-page":"284","article-title":"Antidepressants in irritable bowel syndrome: a systematic review and meta\u2010analysis of randomized controlled trials","volume":"38","author":"Temido MJ","year":"2025","journal-title":"Ann Gastroenterol"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415\u2010025\u201013138\u20105"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.70132"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2025.1621658"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2025.107996"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2025.1507545"},{"issue":"2","key":"e_1_2_11_46_1","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.202012188","article-title":"Targeted attenuation of elevated histone marks at SNCA alleviates alpha\u2010synuclein in Parkinson's disease","volume":"13","author":"Guhathakurta S","year":"2021","journal-title":"EMBO Mol Med"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/tpj.2017.29"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.3300\u201012.2012"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010023\u201047997\u20107"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2018.00290"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1136\/gpsych\u20102025\u2010102229"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2024.111164"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1136\/gpsych\u20102024\u2010101855"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1136\/gpsych\u20102024\u2010101900"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.3171\/2022.9.jns221640"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/2711365"}],"container-title":["General Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gps3.70067","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/gps3.70067","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gps3.70067","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T09:29:51Z","timestamp":1791883791000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gps3.70067"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":55,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/gps3.70067"],"URL":"https:\/\/doi.org\/10.1002\/gps3.70067","archive":["Portico"],"relation":{},"ISSN":["2096-5923","2517-729X"],"issn-type":[{"value":"2096-5923","type":"print"},{"value":"2517-729X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2025-12-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70067"}}